This proposal requests support for predoctoral training in Pharmacological Sciences at the Weill Graduate School of Medical Sciences (WGSMC). The Training Program in Pharmacological Sciences at WGSMS is inter-departmental and inter-institutional, comprising a faculty of distinguished investigators assembled from the Weill Medical College of Cornell University and the Sloan-Kettering Institute. These institutions provide an exceedingly rich research environment, including state-of-the-art instrumentation and core facilities, generous space allocation to the Pharmacology Program and a continuing commitment to recruiting the brightest and best new faculty. The twenty-four participating faculty mentors are a cohesive group of world-class investigators with a strong record for training productive young scientists. The faculty have diverse research interests, providing broad opportunities for training in areas spanning molecular, cellular and systems pharmacology. Primary research areas include computational biology, chemical and structural biology, cell signaling, cardiovascular, antimicrobial, cancer and neuropharmacology. The Program enrolls 10-12 of the most outstanding students annually, with 8-10 typically eligible for NIH support. The incoming Class of 2005 will contain 8 students (of 10 entering;selected from a pool of 114 applicants) that are training-eligible. These recruited students received undergraduate degrees from top universities in the USA, had prior research experiences, mean undergraduate GPAs of 3.75 and mean GRE scores in the 75th percentile. Acceptance of such outstanding students is currently limited by financial resources, not the quality of the applicant pool. Moreover, in accord with NIH guidelines, other institutional training grants have, in recent years, diminished their support for predoctoral trainees, favoring instead the support of postdoctoral trainees. During the first year of predoctoral training, students will complete three laboratory rotations and an intensive curriculum of coursework designed to provide a solid foundation in the areas of science that are fundamental to the discipline of Pharmacology;these include chemical biology, molecular signal transduction, systems pharmacology/physiology, neuropharmacology and cancer pharmacology. The program additionally provides training in logic and experimental design as well as ethics in scientific research. Programs are in place to identify under-represented minority trainees and the Program has been highly successful in recruiting minority trainees. Indeed 3 of the 10 students committed to enter the Program in 2005 are minority candidates (2 are training-eligible). An emphasis of the Program is to cultivate the students'capacity for critical interpretation of scientific literature. This is achieved largely in an intensive small group setting wherein students are rigorously trained in the scientific method and to freely challenge established dogma.